The mechanism(s) of cyst formation in the mammalian kidney is poorly understood, and access to human material for direct studies of nephron function is precluded by the kidney's deep anatomical location. Consequently, this study will utilize animal models of cystic renal disease to examine characteristics of nephron and cyst wall structure and function. Renal cysts will be induced in rats (1) by trauma-scarring of the renal cortex with a hot needle, (2) by dietary exposure to chemicals--diphenylamine, diphenyl thiazol, and nordihydroguaiaretic acid, and (3) by genetic selection, using a newly established strain of rats which transmit renal cystic disease as a apparent dominant trait. Microdissection, light and electron microscopy, and micropuncture will be used to examine structure and function, including hydrostatic pressure, transit times, insulin TF/P ratios, and selected solute and water transport in, along, and out of dilating and cystic nephrons in these models. Results will be analyzed and contrasted to establish (a) the suitability of these preparations as models of human disease, (b) a better understanding of what conditions prevail in a kidney destined for cystic destruction, and (c) the similarities and differences which exist among the models themselves. Enhanced understanding of the mechanism(s) by which cysts form in the mammalian kidney is the major long-range goal of this study.